Midwave resonant cavity infrared detectors (RCIDs) with suppressed background noise.

We report a resonant cavity infrared detector (RCID) with an InAsSb/InAs superlattice absorber with a thickness of only ≈ 100 nm, a 33-period GaAs/Al0.92Ga0.08As distributed Bragg reflector bottom mirror, and a Ge/SiO2/Ge top mirror. At a low bias voltage of 150 mV, the external quantum efficiency (EQE) reaches 58% at the resonance wavelength λres ≈ 4.6 µm, with linewidth δλ = 19-27 nm. The thermal background current for a realistic system scenario with f/4 optic that views a 300 K scene is estimated by integrating the photocurrent generated by background spanning the entire mid-IR spectral band (3-5 µm). The resulting specific detectivity is a factor of 3 lower than for a state-of-the-art broadband HgCdTe device at 300 K, where dark current dominates the noise. However, at 125 K where the suppression of background noise becomes critical, the estimated specific detectivity D* of 5.5 × 1012 cm Hz½/W is more than 3× higher. This occurs despite a non-optimal absorber cut-off that causes the EQE to decrease rapidly with decreasing temperature, e.g., to 33% at 125 K. The present RCID's advantage over the broadband device depends critically on its low EQE at non-resonance wavelengths: ≤ 1% in the range 3.9-5.5 µm. Simulations using NRL MULTIBANDS indicate that impact ionization in the bottom contact and absorber layers dominates the dark current at near ambient temperatures. We expect future design modifications to substantially enhance D* throughout the investigated temperature range of 100-300 K.

Mid-infrared interband cascade light emitting devices grown on off-axis silicon substrates.

The high-quality growth of midwave infrared light emitters on silicon substrates will advance their incorporation into photonic integrated circuits, and also introduce manufacturing advantages over conventional devices grown on lattice-matched GaSb. Here we report interband cascade light emitting devices (ICLEDs) grown on 4 degree offcut silicon with 12% lattice mismatch. Four wafers produced functioning devices, with variations from wafer to wafer but uniform performance of devices from a given wafer. The full width at half maxima for the (004) GaSb rocking curves were as narrow as ∼ 163 arc seconds, and the root mean square surface roughness as small as 3.2 nm. Devices from the four wafers, as well as from a control structure grown to the same design on GaSb, were mounted epitaxial-side-up (epi-up). While core heating severely limited continuous wave (cw) emission from the control devices at relatively modest currents, efficient heat dissipation via the substrate allowed output from the devices on silicon to increase up to much higher currents. Although the devices on silicon had higher leakage currents, probably occurring primarily at dislocations resulting from the lattice-mismatched growth, accounting for differences in architecture the efficiency at high cw current was approximately 75% of that of our previous best-performing standard epi-down ICLEDs grown on GaSb. At 100 mA injection current, 200-µm-diameter mesas produced 184 µW of cw output power when operated at T = 25 °C, and 140 µW at 85°C. Epi-up mid-IR light emitters grown on silicon will be far simpler to process and much less expensive to manufacture than conventional devices grown on GaSb and mounted epi-down.

Methane detection using an interband-cascade LED coupled to a hollow-core fiber.

Midwave infrared interband-cascade light-emitting devices (ICLEDs) have the potential to improve the selectivity, stability, and sensitivity of low-cost gas sensors. We demonstrate a broadband direct absorption CH4 sensor with an ICLED coupled to a plastic hollow-core fiber (1 m length, 1500 µm inner diameter). The sensor achieves a 1σ noise equivalent absorption of approximately 0.2 ppmv CH4 at 1 Hz, while operating at a low drive power of 0.5 mW. A low-cost sub-ppmv CH4 sensor would make monitoring emissions more affordable and more accessible for many relevant industries, such as the petroleum, agriculture, and waste industries.

Interband Cascade Photonic Integrated Circuits on Native III-V Chip.

We describe how a midwave infrared photonic integrated circuit (PIC) that combines lasers, detectors, passive waveguides, and other optical elements may be constructed on the native GaSb substrate of an interband cascade laser (ICL) structure. The active and passive building blocks may be used, for example, to fabricate an on-chip chemical detection system with a passive sensing waveguide that evanescently couples to an ambient sample gas. A variety of highly compact architectures are described, some of which incorporate both the sensing waveguide and detector into a laser cavity defined by two high-reflectivity cleaved facets. We also describe an edge-emitting laser configuration that optimizes stability by minimizing parasitic feedback from external optical elements, and which can potentially operate with lower drive power than any mid-IR laser now available. While ICL-based PICs processed on GaSb serve to illustrate the various configurations, many of the proposed concepts apply equally to quantum-cascade-laser (QCL)-based PICs processed on InP, and PICs that integrate III-V lasers and detectors on silicon. With mature processing, it should become possible to mass-produce hundreds of individual PICs on the same chip which, when singulated, will realize chemical sensing by an extremely compact and inexpensive package.

Scalable in operando strain tuning in nanophotonic waveguides enabling three-quantum-dot superradiance.

The quest for an integrated quantum optics platform has motivated the field of semiconductor quantum dot research for two decades. Demonstrations of quantum light sources, single photon switches, transistors and spin-photon interfaces have become very advanced. Yet the fundamental problem that every quantum dot is different prevents integration and scaling beyond a few quantum dots. Here, we address this challenge by patterning strain via local phase transitions to selectively tune individual quantum dots that are embedded in a photonic architecture. The patterning is implemented with in operando laser crystallization of a thin HfO2 film 'sheath' on the surface of a GaAs waveguide. Using this approach, we tune InAs quantum dot emission energies over the full inhomogeneous distribution with a step size down to the homogeneous linewidth and a spatial resolution better than 1 µm. Using these capabilities, we tune multiple quantum dots into resonance within the same waveguide and demonstrate a quantum interaction via superradiant emission from three quantum dots.

Tunable Coupling of a Double Quantum Dot Spin System to a Mechanical Resonator.

The interaction of quantum systems with mechanical resonators is of practical interest for applications in quantum information and sensing and also of fundamental interest as hybrid quantum systems. Achieving a large and tunable interaction strength is of great importance in this field as it enables controlled access to the quantum limit of motion and coherent interactions between different quantum systems. This has been challenging with solid state spins, where typically the coupling is weak and cannot be tuned. Here we use pairs of coupled quantum dots embedded within cantilevers to achieve a high coupling strength of the singlet-triplet spin system to mechanical motion through strain. Two methods of achieving strong, tunable coupling are demonstrated. The first is through different strain-induced energy shifts for the two QDs when the cantilever vibrates, resulting in changes to the exchange interaction. The second is through a laser-driven AC Stark shift that is sensitive to strain-induced shifts of the optical transitions. Both of these mechanisms can be tuned to zero with electrical bias or laser power, respectively, and give large spin-mechanical coupling strengths.

Resonant-cavity infrared detector with five-quantum-well absorber and 34% external quantum efficiency at 4 µm.

We report resonant-cavity infrared detectors with 34% external quantum efficiency at room temperature at the resonant wavelength of 4.0 µm, even though the absorber consists of only five quantum wells with a total thickness of 50 nm. The full width at half maximum (FWHM) linewidth is 46 nm, and the peak absorption is enhanced by nearly a factor of 30 over that for a single pass through the absorber. In spite of an unfavorable Shockley-Read lifetime in the current material, the dark current density is at the level of state-of-the-art HgCdTe detectors as quantified by "Rule 07." The Johnson-noise limited detectivity (D*) at 21°C is 7 × 109 cm Hz½/W. We expect that future improvements in the device design and material quality will lead to higher quantum efficiency, as well as a significant reduction of the dark current density consistent with the very thin absorber.

Near-infrared frequency comb generation in mid-infrared interband cascade lasers.

The interband cascade laser (ICL) is an ideal candidate for low-power mid-infrared frequency comb spectroscopy. In this work, we demonstrate that its intracavity second-order optical nonlinearity induces a coherent up-conversion of the generated mid-infrared light to the near-infrared through second-harmonic and sum-frequency generation. At 1.8 µm, 10 mW of light at 3.6 µm convert into sub-nanowatt levels of optical power, spread across 30 nm of spectral coverage. The observed linear-to-nonlinear conversion efficiency exceeds ${3\;{\unicode{x00B5} {\rm W/W}}^2}$3µW/W2 in continuous wave operation. We use a dual-band ICL frequency comb source to characterize water vapor absorption in both spectral bands.

Mid-infrared dual-comb spectroscopy with interband cascade lasers.

Two semiconductor optical frequency combs, consuming less than 1 W of electrical power, are used to demonstrate high-sensitivity mid-infrared dual-comb spectroscopy in the important 3-4 µm spectral region. The devices are 4 mm long by 4 µm wide, and each emits 8 mW of average optical power. The spectroscopic sensing performance is demonstrated by measurements of methane and hydrogen chloride with optical multi-pass cell sensitivity enhancement. The system provides a spectral coverage of 33 cm-1 (1 THz), 0.32 cm-1 (9.7 GHz) frequency sampling interval, and peak signal-to-noise ratio of ∼100 at 100 µs integration time. The monolithic design, low drive power, and direct generation of mid-infrared radiation are highly attractive for portable broadband spectroscopic instrumentation in future terrestrial and space applications.

Compact photoacoustic module for methane detection incorporating interband cascade light emitting device.

A photoacoustic module (PAM) for methane detection was developed by combining a novel 3.2 µm interband cascade light emitting device (ICLED) with a compact differential photoacoustic cell. The ICLED with a 22-stage interband cascade active core emitted a collimated power of ~700 µW. A concave Al-coat reflector was positioned adjacent to the photoacoustic cell to enhance the gas absorption length. Assembly of the ICLED and reflector with the photoacoustic cell resulted in a robust and portable PAM without any moving parts. The PAM performance was evaluated in terms of operating pressure, sensitivity and linearity. A 1σ detection limit of 3.6 ppmv was achieved with a 1-s integration time.

Salvage therapy for acute chemorefractory leukemia by allogeneic stem cell transplantation: the Korean experience.

Little is known about the characteristics that make patients with acute leukemia suitable for undergoing salvage therapy by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we analyzed the clinical outcomes of 223 patients with acute leukemia who underwent allo-HSCT while not in complete remission (CR). The primary end points were overall survival (OS) and CR rate. CR was achieved in 79.8% of patients after allo-HSCT. Acute graft-versus-host disease (GVHD) was significantly associated with CR (P = 0.045). During a median follow-up of 30.1 months, the median OS was 6.1 months. OS was significantly longer in patients with good or standard risk cytogenetic characteristics than in those with poor risk cytogenetic characteristics (P = 0.029, P = 0.030, respectively). Patients who received allo-HSCT from a matched sibling donor had better survival than those with unrelated donors (P = 0.015). Primary chemorefractoriness was not associated with poor survival (P = 0.071). The number of chemotherapies before allo-HSCT was significantly correlated with outcome (P = 0.006). Chronic GVHD was a strong predictor of a longer OS (P = 0.025). In conclusion, survival of patients with primary chemorefractory acute leukemia is not lower when treated upfront with allo-HSCT. Hence, allo-HSCT should be actively considered in such patients. Acute and chronic GVHD is associated with better outcomes patients with acute leukemia who have undergone allo-HSCT and not achieved CR.

Prognostic Value of the Pretreatment Advanced Lung Cancer Inflammation Index (ALI) in Diffuse Large B Cell Lymphoma Patients Treated with R-CHOP Chemotherapy.

BACKGROUND: The Advanced Lung Cancer Inflammation Index (ALI, body mass index × albumin/neutrophil-to-lymphocyte ratio) has been demonstrated to be a prognostic factor of survival in some solid cancers. We retrospectively investigated the usefulness of the ALI to predict chemotherapy response and survival in 212 patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. METHODS: Patients were allocated to a low ALI group (n = 82, 38.7%) or a high ALI group (n = 130, 61.3%) according to an optimal pretreatment ALI cut-off value of 15.5 as determined by receiver operating curve analysis. RESULTS: The low ALI group displayed more adverse clinical characteristics, lower rates of complete remission (54.9 vs. 75.4%, p = 0.008), and poorer 5-year progression-free (PFS, 58.1 vs. 77.3%, p = 0.006) and overall (OS, 64.2 vs. 80.2%, p = 0.008) survival. Multivariate analysis showed that low ALI was found to independently predict shorter PFS and OS. Interestingly, a low ALI reverted to a high ALI during treatment in 58 patients (27.4%), and the 5-year OS of these patients was better than that of patients whose ALI remained low (n = 24, 72.5 vs. 24%, p < 0.001). CONCLUSIONS: ALI might be an easily available marker for predicting clinical outcomes in DLBCL patients treated with R-CHOP chemotherapy.

Clinical Outcome and Predictive Factors in the Response to Splenectomy in Elderly Patients with Primary Immune Thrombocytopenia: A Multicenter Retrospective Study.

BACKGROUND: Because many physicians seem reluctant to recommend splenectomy for elderly patients with immune thrombocytopenia (ITP), we investigated the safety and efficacy of splenectomy and the predictive factors for response in these patients. METHODS: 184 patients with primary ITP were retrospectively analyzed based on age at splenectomy: an elderly group (≥60 years, n = 52) and a younger group (<60 years, n = 132). RESULTS: There was no difference in the response rate of elderly versus younger patients (80.7 vs. 80.3%, p = 0.466). Relapse (45.2 vs. 22.6%, p = 0.006), complications, and median postoperative stay (9.5 vs. 7 days, p = 0.019) were significantly higher in the elderly group. The 5-year relapse-free survival of responders was 51.8% in the elderly group and 76.3% in the younger group (p = 0.002). Response to any treatment before splenectomy (HR 2.9, 95% CI: 1.24-6.80, p = 0.014) and platelet count on postoperative day 14 ≥200 × 109/l (HR 31.43, 95% CI: 4.15-238.28, p = 0.001) were independent factors for a favorable response. CONCLUSIONS: Age ≥60 years did not influence the response to splenectomy but was associated with increased relapse and postoperative complications. Splenectomy could provide a durable long-term response for elderly ITP patients.

Spectral narrowing and stabilization of interband cascade laser by volume Bragg grating.

A volume Bragg grating recorded in photo-thermo-refractive glass was used to spectrally lock the emission from an 18-µm-wide interband cascade laser ridge to a wavelength of 3.12 µm. The spectral width of emission into the resonant mode is narrowed by more than 300 times, and the thermal wavelength shift is reduced by 60 times. While the power loss penalty is about 30%, the spectral brightness increases by 200 times.

Factor V Deficiency in Korean Patients: Clinical and Laboratory Features, Treatment, and Outcome.

Due to rarity of factor V (FV) deficiency, there have been only a few case reports in Korea. We retrospectively analysed the clinical-laboratory features of FV deficiency in 10 Korean patients. Between January 1987 and December 2013, 10 case reports published in a Korean journal or proceedings of Korea Society on Thrombosis and Hemostasis were reviewed. Severity is defined as mild (> 5% of factor activity), moderate (1%-5%), and severe (< 1%). The median age at diagnosis, six males and four females, was 26 years (range, 1 month-73 years). Six of 10 patients were classified as moderate, three as mild, and one as severe disease. Eight patients were diagnosed as inherited FV deficiency. The most frequent symptoms were mucosal tract bleedings (40%) such as epistaxis, and menorrhagia in female. Hemarthroses and postoperative bleeding occurred in one and four patients, respectively. Life-threatening bleeding episodes occurred in the peritoneal cavity (n = 2), central nerve system (n = 1), and retroperitoneal space (n = 1). No lethal haemorrhages happened to patients with mild disease. The majority of bleeding episodes were controlled with local measures and fresh-frozen plasma replacement. Two acquired FV deficient-patients showing life-threatening haemorrhages received the immunosuppressive therapy, but one of them died from postoperative bleeding complications. Despite the small sample size of this study due to rarity of the disease, we found that Korean patients with FV deficiency had similar clinical manifestations and treatment outcomes shown in previous studies.

Prevalence and Relationships of Iron Deficiency Anemia with Blood Cadmium and Vitamin D Levels in Korean Women.

Anemia, iron deficiency (ID), and iron deficiency anemia (IDA) are common disorders. This study was undertaken to determine the prevalence of anemia, ID, and IDA in Korean females. We examined the associations between IDA, heavy metals in blood, vitamin D level and nutritional intakes. The study was performed using on data collected from 10,169 women (aged ≥ 10 yr), including 1,232 with anemia, 2,030 with ID, and 690 with IDA during the fifth Korea National Health and Nutrition Examination Survey (KNHANES V; 2010-2012). Prevalence and 95% confidence intervals were calculated, and path analysis was performed to identify a multivariate regression model incorporating IDA, heavy metals in blood, vitamin D level, and nutritional intakes. The overall prevalence of anemia, ID and IDA was 12.4%, 23.11%, and 7.7%, respectively. ID and IDA were more prevalent among adolescents (aged 15-18 yr; 36.5% for ID; 10.7% for IDA) and women aged 19-49 yr (32.7% for ID; 11.3% for IDA). The proposed path model showed that IDA was associated with an elevated cadmium level after adjusting for age and body mass index (ß=0.46, P<0.001). Vitamin D levels were found to affect IDA negatively (ß=-0.002, P<0.001). This study shows that the prevalence of anemia, ID, and IDA are relatively high in late adolescents and women of reproductive age. Path analysis showed that depressed vitamin D levels increase the risk of IDA, and that IDA increases cadmium concentrations in blood. Our findings indicate that systematic health surveillance systems including educational campaigns and well-balanced nutrition are needed to control anemia, ID, and IDA.

Allogeneic clonal mesenchymal stem cell therapy for refractory graft-versus-host disease to standard treatment: a phase I study.

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose (1×10(6) cells/kg), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.

High-power continuous-wave interband cascade lasers with 10 active stages.

We report the pulsed and continuous wave (cw) performance of 10-stage interband cascade lasers (ICLs) emitting at both λ ≈3.2 µm and λ ≈3.45 µm. The slope efficiency is higher while the external differential quantum efficiency per stage remains about the same when comparison is made to earlier results for 7-stage ICLs with similar carrier-rebalanced designs. At T = 25°C, an 18-µm-wide ridge with 4.5 mm cavity length and high-reflection/anti-reflection coatings emits up to 464 mW of cw output power with beam quality factor M(2) = 1.9, for higher brightness than has ever been reported previously for an ICL. When the cavity length is reduced to 1 mm, both the 10-stage and 7-stage devices reach 18% cw wallplug efficiency at T = 25°C.

Pulsed and CW performance of 7-stage interband cascade lasers.

We report a narrow-ridge interband cascade laser emitting at λ ≈3.5 µm that produces up to 592 mW of cw power with a wallplug efficiency of 10.1% and beam quality factor of M(2) = 3.7 at T = 25 °C. A pulsed cavity length study of broad-area lasers from the same wafer confirms that the 7-stage structure with thicker separate confinement layers has a reduced internal loss of ≈3 cm(-1). More generally, devices from a large number of wafers with similar 7-stage designs and wavelengths spanning 2.95-4.7 µm exhibit consistently higher pulsed external differential quantum efficiencies than earlier state-of-the-art ICLs.

Deferasirox improves hematologic and hepatic function with effective reduction of serum ferritin and liver iron concentration in transfusional iron overload patients with myelodysplastic syndrome or aplastic anemia.

BACKGROUND: Transfusional iron overload and its consequences are challenges in chronically transfused patients with myelodysplastic syndromes (MDSs) or aplastic anemia (AA). STUDY DESIGN AND METHODS: This was a prospective, multicenter, open-label study to investigate the efficacy of deferasirox (DFX) by serial measurement of serum ferritin (S-ferritin) level, liver iron concentration (LIC) level using relaxation rates magnetic resonance imaging, and other laboratory variables in patients with MDS or AA. RESULTS: A total of 96 patients showing S-ferritin level of at least 1000 ng/mL received daily DFX for up to 1 year. At the end of the study, S-ferritin level was significantly decreased in MDS (p=0.02366) and AA (p=0.0009). LIC level was also significantly reduced by more than 6.7 mg Fe/g dry weight from baseline. Hemoglobin level and platelet counts were significantly increased from baseline (p=0.002 and p=0.025, respectively) for patients showing significant anemia or thrombocytopenia. Elevated alanine aminotransferase was also significantly decreased from baseline. CONCLUSIONS: This study shows that DFX is effective in reducing S-ferritin and LIC level in transfusional iron overload patients with MDS or AA and is well tolerated. In addition, positive effects in hematologic and hepatic function can be expected with DFX. Iron chelation treatment should be considered in transfused patients with MDS and AA when transfusion-related iron overload is documented.